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Background: To determine whether exosomal microRNAs (miRNAs) in CSF of patients with FTD can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic FTD Initiative (GENFI) cohort and in sporadic FTD. Methods: GENFI participants were either carriers of a pathogenic mutation or at risk of carrying a mutation because a first-degree relative was a symptomatic mutation carrier. Exosomes were isolated from CSF of 23 -pre-symptomatic and 15 symptomatic mutation carriers, and 11 healthy non-mutation carriers. Expression of miRNAs was measured using qPCR arrays. MiRNAs differentially expressed in symptomatic compared to pre-symptomatic mutation carriers were evaluated in 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer’s disease (AD), and 10 healthy controls (HCs). Results: In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared to pre-symptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 [90% CI: 0.79-0.98] and 0.81 [90% CI: 0.68-0.93], and when combined an area of 0.93 [90% CI: 0.87-0.99]. In sporadic FTD, only miR-632 was significantly decreased compared to sporadic AD and HCs. Decrease of miR-632 revealed an area of 0.89 [90% CI: 0.80-0.98]. Conclusions: Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.
Tomato (Solanum lycopersicum) fruit quality and yield are highly dependent on adequate uptake of nutrients. Potassium, magnesium and calcium are essential elements that influence fruit quality traits such as colour, uniformity of ripening, hollow fruit, fruit shape, firmness and acidity. Sodium is not an essential element for tomato and can detrimentally compete with the absorption of potassium and calcium. Daily intakes of potassium, magnesium and calcium in human diets are typically below healthful levels, while sodium intake is often excessive. The objective of this study was to compare 52 diverse commercially important varieties of tomato for concentrations of potassium, magnesium, calcium and sodium in fruits. The tomatoes were produced in replicated plots in Geneva, NY in 2010 and 2011. Multiple fruits per plot were harvested vine-ripe, homogenized and assayed for cations. Analysis of variance showed significant differences among the 52 varieties for all four traits, i.e. cation concentrations (df = 51, P < 0.0001–0.0034) and no significant differences between years for any trait (df = 1, P = 0.3432–0.6770). Factor analysis showed a strong interrelationship between potassium and magnesium that was independent of calcium and sodium. Potassium and magnesium were highly significantly correlated with each other (r = 0.64, P < 0.0001). No other correlations between pairs of traits were observed. Results supported a genetic basis for potassium, magnesium, calcium and sodium concentrations that was consistent across environments (i.e. years). Results can contribute to the development of cultivars with favourable cation profiles in terms of human health and fruit quality.
Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset.
Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA.
Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) < 0.01]. The structure of EPDS responses significantly differed between Europe and the USA (∆*CFI > 0.01), but not between European countries (∆*CFI < 0.01).
Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.
Epidemiology formed the basis of ‘the Barker hypothesis’, the concept of ‘developmental programming’ and today’s discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.
We prove that triangular configurations are plentiful in large subsets of Cartesian squares of finite quasirandom groups from classes having the quasirandom ultraproduct property, for example the class of finite simple groups. This is deduced from a strong double recurrence theorem for two commuting measure-preserving actions of a minimally almost periodic (not necessarily amenable or locally compact) group on a (not necessarily separable) probability space.
Many adults with autism spectrum disorder (ASD) remain undiagnosed. Specialist assessment clinics enable the detection of these cases, but such services are often overstretched. It has been proposed that unnecessary referrals to these services could be reduced by prioritizing individuals who score highly on the Autism-Spectrum Quotient (AQ), a self-report questionnaire measure of autistic traits. However, the ability of the AQ to predict who will go on to receive a diagnosis of ASD in adults is unclear.
We studied 476 adults, seen consecutively at a national ASD diagnostic referral service for suspected ASD. We tested AQ scores as predictors of ASD diagnosis made by expert clinicians according to International Classification of Diseases (ICD)-10 criteria, informed by the Autism Diagnostic Observation Schedule-Generic (ADOS-G) and Autism Diagnostic Interview-Revised (ADI-R) assessments.
Of the participants, 73% received a clinical diagnosis of ASD. Self-report AQ scores did not significantly predict receipt of a diagnosis. While AQ scores provided high sensitivity of 0.77 [95% confidence interval (CI) 0.72–0.82] and positive predictive value of 0.76 (95% CI 0.70–0.80), the specificity of 0.29 (95% CI 0.20–0.38) and negative predictive value of 0.36 (95% CI 0.22–0.40) were low. Thus, 64% of those who scored below the AQ cut-off were ‘false negatives’ who did in fact have ASD. Co-morbidity data revealed that generalized anxiety disorder may ‘mimic’ ASD and inflate AQ scores, leading to false positives.
The AQ's utility for screening referrals was limited in this sample. Recommendations supporting the AQ's role in the assessment of adult ASD, e.g. UK NICE guidelines, may need to be reconsidered.
We have successfully demonstrated optical aperture synthesis at the 4-m Anglo-Australian Telescope. By using a multi-hole mask over the (re-imaged) primary mirror and recording the resulting fringe patterns with high time resolution, diffraction-limited images of sufficiently bright objects can be reconstructed. The data processing uses closure phases to overcome the effects of atmospheric turbulence. We show an image of the double star η Oph, with component separation 0″.45.
Several outbreaks of hepatitis A in men who have sex with men (MSM) were reported in the 1980s and 1990s in Australia and other countries. An effective hepatitis A virus (HAV) vaccine has been available in Australia since 1994 and is recommended for high-risk groups including MSM. No outbreaks of hepatitis A in Australian MSM have been reported since 1996. In this study, we aimed to estimate HAV transmissibility in MSM populations in order to inform targets for vaccine coverage in such populations. We used mathematical models of HAV transmission in a MSM population to estimate the basic reproduction number (R0) and the probability of an HAV epidemic occurring as a function of the immune proportion. We estimated a plausible range for R0 of 1·71–3·67 for HAV in MSM and that sustained epidemics cannot occur once the proportion immune to HAV is greater than ~70%. To our knowledge this is the first estimate of R0 and the critical population immunity threshold for HAV transmission in MSM. As HAV is no longer endemic in Australia or in most other developed countries, vaccination is the only means of maintaining population immunity >70%. Our findings provide impetus to promote HAV vaccination in high-risk groups such as MSM.
This paper presents an integrated design and costing method for large stiffened panels for the purpose of investigating the influence and interaction of lay-up technology and production rate on manufacturing cost. A series of wing cover panels (≈586kg, 19·9m2) have been sized with realistic requirements considering manual and automated lay-up routes. The integrated method has enabled the quantification of component unit cost sensitivity to changes in annual production rate and employed equipment maximum deposition rate. Moreover the results demonstrate the interconnected relationship between lay-up process and panel design, and unit cost. The optimum unit cost solution when using automated lay-up is a combination of the minimum deposition rate and minimum number of lay-up machines to meet the required production rate. However, the location of the optimum unit cost, at the boundaries between the number of lay-up machines required, can make unit cost very sensitive to small changes in component design, production rate, and equipment maximum deposition rate.
An analysis was undertaken to measure age-specific vaccine effectiveness (VE) of 2010/11 trivalent seasonal influenza vaccine (TIV) and monovalent 2009 pandemic influenza vaccine (PIV) administered in 2009/2010. The test-negative case-control study design was employed based on patients consulting primary care. Overall TIV effectiveness, adjusted for age and month, against confirmed influenza A(H1N1)pdm 2009 infection was 56% (95% CI 42–66); age-specific adjusted VE was 87% (95% CI 45–97) in <5-year-olds and 84% (95% CI 27–97) in 5- to 14-year-olds. Adjusted VE for PIV was only 28% (95% CI −6 to 51) overall and 72% (95% CI 15–91) in <5-year-olds. For confirmed influenza B infection, TIV effectiveness was 57% (95% CI 42–68) and in 5- to 14-year-olds 75% (95% CI 32–91). TIV provided moderate protection against the main circulating strains in 2010/2011, with higher protection in children. PIV administered during the previous season provided residual protection after 1 year, particularly in the <5 years age group.
Fifty years after the hyporheic zone was first defined (Orghidan, 1959), there are still gaps in the knowledge regarding the role of biodiversity in hyporheic processes. First, some methodological questions remained unanswered regarding the interactions between biodiversity and physical processes, both for the study of habitat characteristics and interactions at different scales. Furthermore, many questions remain to be addressed to help inform our understanding of invertebrate community dynamics, especially regarding the trophic niches of organisms, the functional groups present within sediment, and their temporal changes. Understanding microbial community dynamics would require investigations about their relationship with the physical characteristics of the sediment, their diversity, their relationship with metabolic pathways, their interactions with invertebrates, and their response to environmental stress. Another fundamental research question is that of the importance of the hyporheic zone in the global metabolism of the river, which must be explored in relation to organic matter recycling, the effects of disturbances, and the degradation of contaminants. Finally, the application of this knowledge requires the development of methods for the estimation of hydrological exchanges, especially for the management of sediment clogging, the optimization of self-purification, and the integration of climate change in environmental policies. The development of descriptors of hyporheic zone health and of new metrology is also crucial to include specific targets in water policies for the long-term management of the system and a clear evaluation of restoration strategies.
The material characterization toolbox has recently experienced a number of parallel revolutionary advances, foreshadowing a time in the near future when material scientists can quantify material structure evolution across spatial and temporal space simultaneously. This will provide insight to reaction dynamics in four-dimensions, spanning multiple orders of magnitude in both temporal and spatial space. This study presents the authors’ viewpoint on the material characterization field, reviewing its recent past, evaluating its present capabilities, and proposing directions for its future development. Electron microscopy; atom probe tomography; x-ray, neutron and electron tomography; serial sectioning tomography; and diffraction-based analysis methods are reviewed, and opportunities for their future development are highlighted. Advances in surface probe microscopy have been reviewed recently and, therefore, are not included [D.A. Bonnell et al.: Rev. Modern Phys. in Review]. In this study particular attention is paid to studies that have pioneered the synergetic use of multiple techniques to provide complementary views of a single structure or process; several of these studies represent the state-of-the-art in characterization and suggest a trajectory for the continued development of the field. Based on this review, a set of grand challenges for characterization science is identified, including suggestions for instrumentation advances, scientific problems in microstructure analysis, and complex structure evolution problems involving material damage. The future of microstructural characterization is proposed to be one not only where individual techniques are pushed to their limits, but where the community devises strategies of technique synergy to address complex multiscale problems in materials science and engineering.
A most probable number (MPN) method capable of estimating as few as ten campylobacters per 100 ml of water is described. The method gave results close to those obtained by the viable count method of Miles, Misra & Irwin (1938) with graded suspensions of Campylobacter jejuni. The method was used to test raw water samples: counts were obtained ranging from 10 to 230 campylobacters per 100 ml for 11 of 49 coastal and estuary water samples, and from 10 to 36 campylobacters per 100 ml for 7 of 44 river samples. Campylobacters were isolated from an additional 24 of the ‘negative’ samples by testing 200 ml volumes by glass microfibre filtration and enrichment culture methods. The MPN method should prove to be a useful epidemiological tool particularly suited to the enumeration of campylobacters in particulate fluids.
We estimated the extent of undiagnosed hepatitis C virus (HCV) infection in injecting drug users (IDUs) in Scotland. We used record-linkage to determine HCV diagnosis status for 41 062 current/former IDUs attending drug treatment and support services between 1 April 1995 and 31 March 2006; the extent of undiagnosed HCV infection was estimated by comparing the number HCV-diagnosed to the number HCV-infected (estimated from an unlinked anonymous testing survey of 2141 current/former IDUs). In all, 9145 IDUs (22%) were diagnosed HCV antibody-positive since first attendance at drug services (diagnosis rate of 33·6/1000 person-years, 95% CI 32·7–34·4). By 31 March 2006, of the 19 632 current/former IDUs who had attended drug services and were determined to be living with HCV, an estimated 58% (95% CI 45–62) had not been HCV-diagnosed. It is essential that the deployment of resources for identifying at-risk IDUs with a view to offering antiviral therapy is guided by evidence.
Early worsening of anxiety, agitation and irritability are thought to be
common among people commencing antidepressants, especially for anxiety
disorders. This phenomenon, which may be termed jitteriness/anxiety
syndrome, is cited as an explanation for early treatment failure and
caution in using selective serotonin reuptake inhibitors (SSRIs).
However, we believe that it is inconsistently defined and that robust
evidence to support the phenomenon is lacking.
To review systematically all evidence relating to jitteriness/ anxiety
syndrome to identify: constituent symptoms; medications implicated;
disorders in which it was reported; incidence; time course; management
strategies; relationship of this syndrome to therapeutic response;
distinction between syndrome and akathisia; relationship between syndrome
and suicide; and genetic predispositions.
A systematic search identified articles and these were included in the
review if they addressed one of the above aspects of jitteriness/anxiety
Of 245 articles identified, 107 articles were included for review. No
validated rating scales for jitteriness/anxiety syndrome were identified.
There was no robust evidence that the incidence differed between SSRIs
and tricyclic antidepressants, or that there was a higher incidence in
anxiety disorders. Published incidence rates varied widely from 4 to 65%
of people commencing antidepressant treatment. Common treatment
strategies for this syndrome included a slower titration of
antidepressant and the addition of benzodiazepines. Conclusive evidence
for the efficacy of these strategies is lacking. There was conflicting
and inconclusive evidence as to whether the emergence of this syndrome
had a predictive value on the response to treatment. It appears to be a
separate syndrome from akathisia, but evidence for this assertion was
limited. The effect of jitteriness/anxiety syndrome on suicide rates has
not been evaluated. Three studies examined genetic variations and
side-effects from treatment, but none was specifically designed to assess
Jitteriness/anxiety syndrome remains poorly characterised. Despite this,
clinicians' perception of this syndrome influences prescribing and it is
cited to support postulated mechanisms of drug action. We recommend
systematised evaluation of side-effects at earlier time points in
antidepressant trials to further elucidate this clinically important
The serum antibody titres in 62 cases of acute brucellosis are presented. The antibody persisting after infection and the appearance of non-agglutinating antihuman globulin titres were investigated. The criteria for the serological diagnosis of acute and chronic brucellosis are discussed.
Oesophagus samples from 714 cattle from Western Australia were examined by artificial digestion to detect the presence of Sarcocystis spp. The overall prevalence of infection was 52%. The prevalence of infection increased with age and was highest in the entire males (92%). The prevalence was lower in cattle which originated from arid and semiarid regions (9 and 31% respectively) than those from tropical (87%) and temperate (60%) regions. possible reasons for these differences are discussed and it is concluded that environmental and management factors as well as host age and sex influence the prevalence of infection with Sarcocystis spp. in cattle.
The results are presented of testing untreated producer–retailer herd milk samples for the presence of Brucella abortus during the period 1965–1972 in the North Lancashire region.
There was a steady decline in the incidence of infected herds from 22 % in 1965 to 12% in 1971. A sharp fall to 5% in 1972 suggests that the introduction of the Brucellosis Incentives Scheme and the eradication programme has helped to reduce the practice of selling brucella-infected cattle in the open market which was prevalent in the period 1965 to 1970.
This practice of selling brucella-infected cattle may also be a prime factor in the changing pattern of distribution of the biotypes of B. abortus which was observed during the period 1965 to 1970.
A comparison of the two areas in the region show that the incidence of herd infection was always greater in the area containing flying herds than in the area in which self-contained herds predominated.